Significant impairment of high-dose methotrexate clearance following vancomycin administration in the absence of overt renal impairment

Abstract

Background: Methotrexate is an antimetabolite cytotoxic drug which is predominantly renally excreted. Vancomycin, a glycopeptide antibiotic that is used in the febrile neutropaenic patient, can be nephrotoxic. There are no previous reports of any interactions between these two drugs. Patients and methods: We describe two patients with osteosarcoma treated with high-dose methotrexate-containing chemotherapy who had significantly delayed methotrexate clearance several weeks following exposure to vancomycin. Results: These patients were treated with alternating chemotherapy consisting of 12 g/m2 methotrexate, 60 mg/m2 cisplatin, 75 mg/m2 adriamycin and 15 g/m2 ifosfamide. In both patients, seru..